The Prostate 66:1070 ^1075 (2006) Monomethylated Selenium Inhibits Growth of LNCaP Human Prostate Cancer Xenograft Accompanied by a Decrease in the Expression of Androgen Receptor and Prostate-Specific Antigen (PSA) Soo Ok Lee, Jae Yeon Chun, Nagalakshmi Nadiminty, Donald L. Trump, Clement Ip, Yan Dong, and Allen C. Gao* Departments of Medicine and Pharmacology & Therapeutics,Cancer Prevention, Roswell Park Cancer Institute, Buffalo, NewYork OBJECTIVES. Epidemiological studies and prevention trials suggest selenium is a promising preventive agent for prostate cancer. Selenium-containing compounds inhibited the growth of prostate cancer cell lines including androgen sensitive LNCaP and androgen insensitive DU145 and PC3 cells in vitro. Previous study revealed a novel mechanism of selenium action in which selenium (methylseleninic acid (MSA)) markedly reduced androgen receptor (AR) signaling in prostate cancer cells, suggesting that selenium might act as an antiandrogen, which could serve as a therapeutic agent for prostate cancer. In this study, we tested whether selenium (methylselenocysteine (MSC)) affects tumor growth of human prostate cancer cells by targeting AR signaling in vivo. METHODS. Prostate tumor xenografts were established in nude mice by co-inoculating LNCaP cells with Matrigel. The mice-bearing tumors were treated with or without MSC (100 mg/ mouse/day) via intraperitoneal injection for 2 weeks. The effect of MSC on tumor growth, AR, and prostate-specific antigen (PSA) expression was examined. RESULTS. Methylselenocysteine (MSC) significantly inhibited LNCaP tumor growth (P < 0.05). AR expression in tumor tissues and serum PSA levels were considerably decreased in MSC-treated mice compared to the vehicle controls. CONCLUSIONS. Pharmacological dose of MSC inhibits the growth of LNCaP human prostate cancer in vivo accompanied by a decrease in the expression of AR and PSA. These findings suggest that selenium (MSC) can serve as a therapeutic agent aimed at disruption of AR signaling for prostate cancer. Prostate 66: 1070–1075, 2006. # 2006 Wiley-Liss, Inc. KEY WORDS: selenium; androgen receptor; PSA; prostate cancer INTRODUCTION Accumulating epidemiological and molecular evi- dence suggest that selenium protects against the devel- opment of variety cancers including prostate, colon, esophagus, lung, and gastric cardia [1–4]. Numerous case-control studies have demonstrated an inverse relationship between selenium status and prostate cancer risk [5–9]. A landmark study of selenium as a chemopreventive agent initiated by Larry Clark demon- strated that supplementation of people with selenized yeast (200 mg of selenium) is capable of reducing the overall cancer morbidity by nearly 50% [1]. Patients Abbreviations: AR, androgen receptor; PSA, prostate-specific anti- gen; MSC, methylselenocysteine; MSA, methylseleninic acid. Grant sponsor: NIH; Grant number: CA90271; Grant sponsor: US Army Medical Research Materiel Command AMRMC Prostate Cancer Research Program; Grant number: DAMD17-01-1-0089; Grant sponsor: Roswell Park Alliance Foundation. *Correspondence to: Allen C. Gao, Departments of Medicine and Pharmacology & Therapeutics, Grace Cancer Drug Center, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263. E-mail: allen.gao@roswellpark.org Received 31 March 2005; Accepted 25 May 2005 DOI 10.1002/pros.20329 Published online 24 April 2006 in Wiley InterScience (www.interscience.wiley.com). ß 2006 Wiley-Liss, Inc.